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Genetic Engineering of Mesenchymal Stem Cells for Differential Matrix Deposition on 3D Woven Scaffolds.

Publication ,  Journal Article
Huynh, NPT; Brunger, JM; Gloss, CC; Moutos, FT; Gersbach, CA; Guilak, F
Published in: Tissue engineering. Part A
October 2018

Tissue engineering approaches for the repair of osteochondral defects using biomaterial scaffolds and stem cells have remained challenging due to the inherent complexities of inducing cartilage-like matrix and bone-like matrix within the same local environment. Members of the transforming growth factor β (TGFβ) family have been extensively utilized in the engineering of skeletal tissues, but have distinct effects on chondrogenic and osteogenic differentiation of progenitor cells. The goal of this study was to develop a method to direct human bone marrow-derived mesenchymal stem cells (MSCs) to deposit either mineralized matrix or a cartilaginous matrix rich in glycosaminoglycan and type II collagen within the same biochemical environment. This differential induction was performed by culturing cells on engineered three-dimensionally woven poly(ɛ-caprolactone) (PCL) scaffolds in a chondrogenic environment for cartilage-like matrix production while inhibiting TGFβ3 signaling through Mothers against DPP homolog 3 (SMAD3) knockdown, in combination with overexpressing RUNX2, to achieve mineralization. The highest levels of mineral deposition and alkaline phosphatase activity were observed on scaffolds with genetically engineered MSCs and exhibited a synergistic effect in response to SMAD3 knockdown and RUNX2 expression. Meanwhile, unmodified MSCs on PCL scaffolds exhibited accumulation of an extracellular matrix rich in glycosaminoglycan and type II collagen in the same biochemical environment. This ability to derive differential matrix deposition in a single culture condition opens new avenues for developing complex tissue replacements for chondral or osteochondral defects.

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Published In

Tissue engineering. Part A

DOI

EISSN

1937-335X

ISSN

1937-3341

Publication Date

October 2018

Volume

24

Issue

19-20

Start / End Page

1531 / 1544

Related Subject Headings

  • Transforming Growth Factor beta3
  • Tissue Scaffolds
  • Tissue Engineering
  • Smad3 Protein
  • Osteogenesis
  • Minerals
  • Mesenchymal Stem Cells
  • Humans
  • Glycosaminoglycans
  • Genetic Engineering
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Huynh, N. P. T., Brunger, J. M., Gloss, C. C., Moutos, F. T., Gersbach, C. A., & Guilak, F. (2018). Genetic Engineering of Mesenchymal Stem Cells for Differential Matrix Deposition on 3D Woven Scaffolds. Tissue Engineering. Part A, 24(19–20), 1531–1544. https://doi.org/10.1089/ten.tea.2017.0510
Huynh, Nguyen P. T., Jonathan M. Brunger, Catherine C. Gloss, Franklin T. Moutos, Charles A. Gersbach, and Farshid Guilak. “Genetic Engineering of Mesenchymal Stem Cells for Differential Matrix Deposition on 3D Woven Scaffolds.Tissue Engineering. Part A 24, no. 19–20 (October 2018): 1531–44. https://doi.org/10.1089/ten.tea.2017.0510.
Huynh NPT, Brunger JM, Gloss CC, Moutos FT, Gersbach CA, Guilak F. Genetic Engineering of Mesenchymal Stem Cells for Differential Matrix Deposition on 3D Woven Scaffolds. Tissue engineering Part A. 2018 Oct;24(19–20):1531–44.
Huynh, Nguyen P. T., et al. “Genetic Engineering of Mesenchymal Stem Cells for Differential Matrix Deposition on 3D Woven Scaffolds.Tissue Engineering. Part A, vol. 24, no. 19–20, Oct. 2018, pp. 1531–44. Epmc, doi:10.1089/ten.tea.2017.0510.
Huynh NPT, Brunger JM, Gloss CC, Moutos FT, Gersbach CA, Guilak F. Genetic Engineering of Mesenchymal Stem Cells for Differential Matrix Deposition on 3D Woven Scaffolds. Tissue engineering Part A. 2018 Oct;24(19–20):1531–1544.

Published In

Tissue engineering. Part A

DOI

EISSN

1937-335X

ISSN

1937-3341

Publication Date

October 2018

Volume

24

Issue

19-20

Start / End Page

1531 / 1544

Related Subject Headings

  • Transforming Growth Factor beta3
  • Tissue Scaffolds
  • Tissue Engineering
  • Smad3 Protein
  • Osteogenesis
  • Minerals
  • Mesenchymal Stem Cells
  • Humans
  • Glycosaminoglycans
  • Genetic Engineering